Physiology Flashcards
Apoptosis
Intrinsic pathway = cell exposed to stress (apoptosis intrinsically triggered by the cell)
Extrinsic pathway = apoptosis signal comes from outside of the cell (macrophages or T cells)
Apoptosis: intrinsic
- BAX and BAC proteins pass from cytosol-> mitochondria (pierce it, becomes porous)
–> SMACS and cytochrome C proteins spill OUT of mitochondria in to the cytosol
(A) SMACS binds to proteins that usually inhibit apoptosis -> deactivation
(B) Cytochrome C binds to ATP (energy source) and Apaf-1 enzyme
Cytochrome C + Apaf-1 = formation of apoptosome protein complex
Apaf-1 portion of apoptosome -> pro-caspase 9 cleavage and activation
Caspase cascade ultimately triggers apoptosis
Apoptosis: extrinsic
A) Macrophage mediated extrinsic apoptosis: Nearby macrophage recognises old, redundant or pathogenic cell(s) –> releases TNF-alpha
TNF-alpha: binds to death receptor on target cell membrane
Intracellular death domain of receptor binds to
(Fass associated protein with death domain) FADD, (Tumour necrosis factor receptor type 1- associated death domain protein) AND TRADD
Formation of death inducing signalling complex or DISC –> Cleavage and activation of procaspase 8 in to caspase 8
Again, caspase cascade ultimately triggers apoptosis
B) T cell (cytotoxic) mediated extrinsic apoptosis: Detects that near by cell is expressing foreign antigens
T cell membrane expression of FAS-ligand
FAS-ligand binds to target cell (first apoptosis signal) FAS-receptor (a death receptor)
How do caspase cascade ultimately triggers apoptosis
- Cleavage of cell nucleus, organelles and cytoskeleton
- Cell membrane blebbing
- Sections break off
- Phagocytosed by nearby macrophages
Necrosis
External mechanisms can be responsible:
Infection
Extreme temperature variation
Or internal mechanisms:
Tissue ischaemia
Toxins/ ischaemia damage mitochondria à lack of ATP production (energy source for ion transport)
Disrupted ion pumps at cell membrane à sodium influx and cell swelling à BURSTING
Immune cells attracted by this à necrosis as an inflammatory process
Immune cells release proteases and reactive oxygen species
Unstable reactive oxygen species damage nearby cells in addition
Potential for tissue damage and organ dysfunction
The indications and techniques for feticide
Live birth becomes increasingly common after 21+6 weeks gestation
Where MTOP (fetal delivery) is being performed beyond this point, feticide is routinely recommended to reduce this risk
(can be offered from 20 weeks if woman is worried but not routinely offered)
Intracardiac potassium chloride
Digoxin or lignocaine options but less commonly used
